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pmid:30368515

Identification of Potential Gene Interactions in Heart Failure Caused by Idiopathic Dilated Cardiomyopathy.

Huijuan Huang · Beibei Luo · Boqun Wang · Qianwen Wu · Yuming Liang · Yan He

Medical science monitor : international medical journal of experimental and clinical research · 2018 doi:10.12659/MSM.912984

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30368515
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science-record
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
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2026-11-01T15:40:38Z
updated_at
2026-11-01T22:43:36Z
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paper object · 10 fields
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title
Identification of Potential Gene Interactions in Heart Failure Caused by Idiopathic Dilated Cardiomyopathy.
doi
10.12659/MSM.912984
pmid
30368515
authors array · 6 items
[0]
Huijuan Huang
[1]
Beibei Luo
[2]
Boqun Wang
[3]
Qianwen Wu
[4]
Yuming Liang
[5]
Yan He
journal
Medical science monitor : international medical journal of experimental and clinical research
year
2018
abstract
BACKGROUND Many heart failure (HF) cases are caused by idiopathic dilated cardiomyopathy (iDCM). This study explored the mechanisms of the development and progression of HF caused by iDCM. MATERIAL AND METHODS The gene expression profiles of 102 samples were downloaded from the GEO database (GSE5406). Differentially expressed genes (DEGs) were identified through GO analysis and a KEGG pathway analysis, respectively. A protein-protein interaction (PPI) network was constructed and analyzed to screen potential regulatory proteins. In addition, MCODE and a cytoHubba plugin were used to identify the module and hub genes of DEGs. Finally, transcription factors (TFs) were predicted using PASTAA. We did not perform whole-exome sequencing (WES) for detecting mitochondrial DNA (mtDNA). RESULTS A total of 197 DEGs were screened, and 3 modules, and 4 upregulated and 11 downregulated hub genes were screened. The GO analysis focused on the terms and 12 KEGG pathways were enriched. The FOS, TIMP1, and SERPINE1 hub genes, as well as some key TFs, demonstrated important roles in the progression of HF caused by iDCM. CEBPD, CEBOB, CDC37L1, and SRGN may be new targets for HF in iDCM patients. CONCLUSIONS The identified DEGs and their enriched pathways provide references for exploring the mechanisms of the development and progression of HF patients with iDCM. Moreover, modules, hub genes, and TFs may be useful in the treatment and diagnosis of HF patients with iDCM. However, mtDNA was not investigated.
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A Linear Models for Microarray Data (LIMMA) package of R was used to identify the DEGs in the iDCM-HF samples compared with the normal LV samples [12].
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sections[5] "Identification of DEGs" paragraph 2
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A Linear Models for Microarray Data (LIMMA) package of R was used to identify the DEGs in the iDCM-HF samples compared with the normal LV samples [12].
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The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9].
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null
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sections[3] "Data source" paragraph 2
quote
The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9].
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The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9].
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The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9].
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210
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null
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96
taxon
Homo sapiens
title
Human ischemic cardiomyopathy, idiopathic cardiomyopathy, and nonfailing controls
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2026-11-01T15:39:54Z
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[2] object · 16 fields
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Transcription factor that hub gene expression predicted.
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PMC6216482
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10
section_title
Analysis of TFs
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22
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5
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Table 3
caption
Transcription factor that hub gene expression predicted.
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[0] array · 1 item
[0]
(A) Top 20 TFs of up-regulted hub genes.
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[0]
Rank
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[3]
Association score
[4]
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[0]
1
[1]
E2F1_Q4_01
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3.956
[4]
7.15E-04
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[1]
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3.872
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[1]
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3.829
[4]
9.59E-04
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[1]
ATF6_01
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3.829
[4]
9.59E-04
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[1]
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3.646
[4]
1.45E-03
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6
[1]
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3.237
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3.07E-03
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7
[1]
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3.129
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3.76E-03
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8
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6.02E-03
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[0]
9
[1]
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2.472
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1.59E-02
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[0]
10
[1]
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2.425
[4]
1.84E-02
[12] array · 5 items
[0]
11
[1]
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2.425
[4]
1.84E-02
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[1]
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2.425
[4]
1.92E-02
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[1]
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2.345
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2.11E-02
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3.09E-02
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20
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section[17]/table-wrap[1]#t3-medscimonit-24-7697
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The KEGG pathway(p.adj<0.5).
structure object · 5 fields
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PMC6216482
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13
section_title
Functional enrichment of DEGs
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Table 1
caption
The KEGG pathway(p.adj<0.5).
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[0] array · 4 items
[0]
ID
[1]
Description
[2]
Gene
[3]
P.adj
[1] array · 4 items
[0]
hsa04974
[1]
Protein digestion and absorption
[2]
SLC38A2, ATP1A1, COL1A2, COL15A1, COL21A1, COL1A1, COL3A1, ATP1A3
[3]
0.002989601
[2] array · 4 items
[0]
hsa04978
[1]
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HMOX2, ATP1A1, MT1X, MT1M, MT2A, ATP1A3
[3]
0.002989601
[3] array · 4 items
[0]
hsa05205
[1]
Proteoglycans in cancer
[2]
LUM, MAP2K1, CDKN1A, FLNC, FZD7, ITGA5, PPP1R12B, COL21A1, THBS1, STAT3, MYC
[3]
0.002989601
[4] array · 4 items
[0]
hsa04510
[1]
Focal adhesion
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[3]
0.01037994
[5] array · 4 items
[0]
hsa04151
[1]
PI3K-Akt signaling pathway
[2]
ATF4, FGF1, MAP2K1, COL1A2, CDKN1A, ITGA5, AREG, PDGFD, COL1A1, THBS1, THBS4, MYC, SPP1
[3]
0.020270584
[6] array · 4 items
[0]
hsa04512
[1]
ECM-receptor interaction
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COL1A2, ITGA5, COL1A1, THBS1, THBS4, SPP1
[3]
0.020270584
[7] array · 4 items
[0]
hsa04657
[1]
IL-17 signaling pathway
[2]
FOSL1, S100A9, CEBPB, CCL2, S100A8, FOS
[3]
0.031466966
[8] array · 4 items
[0]
hsa04010
[1]
MAPK signaling pathway
[2]
ATF4, FGF1, MAP2K1, FLNC, AREG, PDGFD, PLA2G4C, MYC, DUSP1, HSPA6, FOS
[3]
0.031466966
[9] array · 4 items
[0]
hsa04933
[1]
AGE-RAGE signaling pathway in diabetic complications
[2]
COL1A2, SERPINE1, COL1A1, STAT3, COL3A1, CCL2
[3]
0.033386478
[10] array · 4 items
[0]
hsa04066
[1]
HIF-1 signaling pathway
[2]
MAP2K1, SERPINE1, CDKN1A, NPPA, STAT3, TIMP1
[3]
0.033386478
[11] array · 4 items
[0]
hsa05219
[1]
Bladder cancer
[2]
MAP2K1, CDKN1A, THBS1, MYC
[3]
0.033386478
[12] array · 4 items
[0]
hsa05224
[1]
Breast cancer
[2]
FGF1, MAP2K1, CDKN1A, FZD7, MYC, HEY1, FOS
[3]
0.044949711
locator
section[13]/table-wrap[1]#t1-medscimonit-24-7697
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asset:table:pmid:30368515:3
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jats-table
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verified
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read_table
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note
The information of 15 hub gene.
structure object · 5 fields
pmcid
PMC6216482
section_index
16
section_title
Hub gene selection
row_count
16
column_count
4
table object · 8 fields
label
Table 2
caption
The information of 15 hub gene.
rows array · 16 items
[0] array · 4 items
[0]
Gene
[1]
FC
[2]
P
[3]
Degree
[1] array · 4 items
[0]
FOS
[1]
0.646836359
[2]
0.011938948
[3]
10
[2] array · 4 items
[0]
MAP2K1
[1]
0.640915732
[2]
1.48E-13
[3]
4
[3] array · 4 items
[0]
FGF1
[1]
1.674161905
[2]
8.91E-14
[3]
3
[4] array · 4 items
[0]
CEBPB
[1]
0.636011871
[2]
0.00000402
[3]
3
[5] array · 4 items
[0]
TNFSF10
[1]
1.687192949
[2]
0.00000229
[3]
2
[6] array · 4 items
[0]
CDC37L1
[1]
0.607610736
[2]
0.000000779
[3]
5
[7] array · 4 items
[0]
ATF4
[1]
0.646899144
[2]
7.88E-14
[3]
4
[8] array · 4 items
[0]
SERPINE1
[1]
0.377215132
[2]
3.06E-11
[3]
7
[9] array · 4 items
[0]
SEPP1
[1]
1.653991537
[2]
0.00000233
[3]
5
[10] array · 4 items
[0]
CDKN1A
[1]
0.561612771
[2]
5.28E-11
[3]
3
[11] array · 4 items
[0]
ISLR
[1]
1.828979092
[2]
3.34E-17
[3]
6
[12] array · 4 items
[0]
SRGN
[1]
0.577572122
[2]
0.000235932
[3]
5
[13] array · 4 items
[0]
FOSL1
[1]
0.56105762
[2]
1.11E-08
[3]
4
[14] array · 4 items
[0]
TIMP1
[1]
0.590064052
[2]
0.000000976
[3]
8
[15] array · 4 items
[0]
CEBPD
[1]
0.559030961
[2]
0.0000465
[3]
3
locator
section[16]/table-wrap[1]#t2-medscimonit-24-7697
[5] object · 16 fields
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asset:table:pmid:30368515:4
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table
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jats-table
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application/vnd.jats.table+json
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sha256:e6042ee7b9df5224fb68ce091bc69208497d87527009c17a0f94221dea4bffec
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read_table
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note
Transcription factor that hub gene expression predicted.
structure object · 5 fields
pmcid
PMC6216482
section_index
17
section_title
Analysis of TFs
row_count
22
column_count
5
table object · 8 fields
label
Table 3
caption
Transcription factor that hub gene expression predicted.
rows array · 22 items
[0] array · 1 item
[0]
(A) Top 20 TFs of up-regulted hub genes.
[1] array · 5 items
[0]
Rank
[1]
Matrix
[2]
Transcription factor
[3]
Association score
[4]
P-Value
[2] array · 5 items
[0]
1
[1]
E2F1_Q4_01
[2]
Dp-1, E2f-1
[3]
3.956
[4]
7.15E-04
[3] array · 5 items
[0]
2
[1]
MTATA_B
[2]
N/A
[3]
3.872
[4]
9.01E-04
[4] array · 5 items
[0]
3
[1]
AHRARNT_01
[2]
Ahr, Arnt
[3]
3.829
[4]
9.59E-04
[5] array · 5 items
[0]
4
[1]
ATF6_01
[2]
Atf6
[3]
3.829
[4]
9.59E-04
[6] array · 5 items
[0]
5
[1]
E2F_Q3_01
[2]
Dp-1, E2f-1
[3]
3.646
[4]
1.45E-03
[7] array · 5 items
[0]
6
[1]
E2F_Q3
[2]
N/A
[3]
3.237
[4]
3.07E-03
[8] array · 5 items
[0]
7
[1]
AP4_Q6
[2]
Ap-4
[3]
3.129
[4]
3.76E-03
[9] array · 5 items
[0]
8
[1]
TAXCREB_02
[2]
Creb, Deltacreb
[3]
2.979
[4]
6.02E-03
[10] array · 5 items
[0]
9
[1]
CBF_01
[2]
N/A
[3]
2.472
[4]
1.59E-02
[11] array · 5 items
[0]
10
[1]
PAX3_01
[2]
Pax-3
[3]
2.425
[4]
1.84E-02
[12] array · 5 items
[0]
11
[1]
USF_Q6_01
[2]
Usf-1, Usf1
[3]
2.425
[4]
1.84E-02
[13] array · 5 items
[0]
12
[1]
PAX3_B
[2]
Pax-3
[3]
2.425
[4]
1.92E-02
[14] array · 5 items
[0]
13
[1]
AP4_Q5
[2]
Ap-4
[3]
2.345
[4]
2.11E-02
[15] array · 5 items
[0]
14
[1]
AP2ALPHA_01
[2]
Ap-2alpha, Ap-2alphaa
[3]
2.327
[4]
2.29E-02
[16] array · 5 items
[0]
15
[1]
AP2GAMMA_01
[2]
Ap-2gamma
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2.327
[4]
2.29E-02
[17] array · 5 items
[0]
16
[1]
SRF_01
[2]
Srf
[3]
2.225
[4]
2.83E-02
[18] array · 5 items
[0]
17
[1]
TCF11MAFG_01
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Lcr-f1, Mafg
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2.158
[4]
3.09E-02
[19] array · 5 items
[0]
18
[1]
E2F1_Q3
[2]
E2f-1
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2.123
[4]
3.53E-02
[20] array · 5 items
[0]
19
[1]
USF_01
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Usf1
[3]
2.116
[4]
3.56E-02
[21] array · 5 items
[0]
20
[1]
E4F1_Q6
[2]
N/A
[3]
2.071
[4]
3.77E-02
locator
section[17]/table-wrap[1]#t3-medscimonit-24-7697
gaps array · 2 items
[0]
asset:data:geo:GSE5406 not downloaded
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asset:data:geo:GSE5406 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
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[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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parameters object · 0 fields
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[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
A Linear Models for Microarray Data (LIMMA) package of R was used to identify the DEGs in the iDCM-HF samples compared with the normal LV samples [12].
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id
method-2
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network_analysis
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label
Network / pathway analysis
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[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
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edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
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gaps array · 0 items
capability object · 3 fields
state
complete
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capability_id
capability:computational_analysis
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[0]
meta_analysis
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machine_learning
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survival_analysis
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statistical_regression
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pca
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molecular_docking
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network_analysis
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differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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state
complete
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R1
blocked_on
nothing:replicable_now
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true
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normalise_counts
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differential_expression_fit
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fdr_bh
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
GSE5406
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[0]
GSE5406
statements array · 1 item
[0]
The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9].
basis
The paper names GSE5406 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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normalise_counts
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differential_expression_fit
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fdr_bh
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source:pmid:30368515
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data:geo:GSE5406
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asset:table:pmid:30368515:1
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asset:table:pmid:30368515:2
[4]
asset:table:pmid:30368515:3
[5]
asset:table:pmid:30368515:4
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run_analysis
must_build object · 5 fields
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data:geo:GSE5406
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partial
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extraction_review
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MiniMax-M3.1-Flash
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minimax
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minimax
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single_reader
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verbatim
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null
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3
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id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
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review.machine_critique
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review.human_critique
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absent
status
not_run
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execution.not_run
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pmid:30368515
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paper
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pmid:30368515
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source:pmid:30368515
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manuscript
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PMID 30368515 full text
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data:geo:GSE5406
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dataset
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GEO GSE5406
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activity-reading-sci-2026-11-01
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classification
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pmid:30368515
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paper
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pmid:30368515
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source:pmid:30368515
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PMID 30368515 full text
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data:geo:GSE5406
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dataset
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GEO GSE5406
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agent:corpus-assay-engine
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activity-read-30368515
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agent:minimax-reader
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activity-resolve-GSE5406
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data:geo:GSE5406
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agent:corpus-assay-engine
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agent:minimax-reader
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2cb3e42f047d2ecf
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pmid:30368515
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sha256:14fd75a1ea89852893cdc47f530c034988361da10af74d414ce07f5fdbd78a03
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null
gaps array · 6 items
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asset:data:geo:GSE5406 licence not read
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review.independent_reader
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[0]
A Linear Models for Microarray Data (LIMMA) package of R was used to identify the DEGs in the iDCM-HF samples compared with the normal LV samples [12].
order_basis
analysis_only
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30368515", "kind": "science-record", "revision": 9, "content_hash": "sha256:bbabfd13a6c5eebf323b104f98140c8b548d39ef9e5d040f45b60e445d982a74", "created_at": "2026-11-01T15:40:38Z", "updated_at": "2026-11-01T22:43:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Potential Gene Interactions in Heart Failure Caused by Idiopathic Dilated Cardiomyopathy.", "doi": "10.12659/MSM.912984", "pmid": "30368515", "authors": ["Huijuan Huang", "Beibei Luo", "Boqun Wang", "Qianwen Wu", "Yuming Liang", "Yan He"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2018, "abstract": "BACKGROUND Many heart failure (HF) cases are caused by idiopathic dilated cardiomyopathy (iDCM). This study explored the mechanisms of the development and progression of HF caused by iDCM. MATERIAL AND METHODS The gene expression profiles of 102 samples were downloaded from the GEO database (GSE5406). Differentially expressed genes (DEGs) were identified through GO analysis and a KEGG pathway analysis, respectively. A protein-protein interaction (PPI) network was constructed and analyzed to screen potential regulatory proteins. In addition, MCODE and a cytoHubba plugin were used to identify the module and hub genes of DEGs. Finally, transcription factors (TFs) were predicted using PASTAA. We did not perform whole-exome sequencing (WES) for detecting mitochondrial DNA (mtDNA). RESULTS A total of 197 DEGs were screened, and 3 modules, and 4 upregulated and 11 downregulated hub genes were screened. The GO analysis focused on the terms and 12 KEGG pathways were enriched. The FOS, TIMP1, and SERPINE1 hub genes, as well as some key TFs, demonstrated important roles in the progression of HF caused by iDCM. CEBPD, CEBOB, CDC37L1, and SRGN may be new targets for HF in iDCM patients. CONCLUSIONS The identified DEGs and their enriched pathways provide references for exploring the mechanisms of the development and progression of HF patients with iDCM. Moreover, modules, hub genes, and TFs may be useful in the treatment and diagnosis of HF patients with iDCM. However, mtDNA was not investigated.", "claims": [{"id": "claim-method", "statement": "A Linear Models for Microarray Data (LIMMA) package of R was used to identify the DEGs in the iDCM-HF samples compared with the normal LV samples [12].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30368515", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "A Linear Models for Microarray Data (LIMMA) package of R was used to identify the DEGs in the iDCM-HF samples compared with the normal LV samples [12]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30368515", "locator": "sections[3] \"Data source\" paragraph 2", "quote": "The gene expression profile of GSE5406 was downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo/) using the platform GPL96 ([HG-U133A] Affymetrix Human Genome U133A Array; Affymetrix, Inc., Santa Clara, CA, USA). A total of 102 individuals were analyzed in this study. RNA samples for this dataset were extracted from explanted left ventricular (LV) myocardia of 86 patients with systolic HF due to iDCM (iDCM-HF), and 16 unused donor hearts with normal LV functions at the time of harvest were used as controls [9]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30368515"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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